Resurgence of Clinical Malaria in Ethiopia in the Era of Anopheles stephensi Invasion.

Background: The invasion of Anopheles stephensi into Africa poses a potential threat to malaria control and elimination on the continent. However, it is not clear if the recent malaria resurgence in Ethiopia has linked to the expansion of An. stephensi. We aimed to summarize the major achievements and lesson learnt in malaria control in Ethiopia from 2001 to 2022, to assess the new challenges and prospects for the control of An. stephensi. Methods and findings: We obtained the clinical malaria case reports, antimalarial drug treatment records, insecticide-treated and long-lasting insecticidal net (ITN/LLIN) distribution and utilization records, and indoor residual spraying (IRS) coverage data from the Ethiopian Ministry of Health (MoH) for the period 2001-2022. We analyzed clinical malaria hotspots using spatially optimized hotspot analysis. We investigated malaria outbreaks in 2022 and examined the potential role of An. stephensi in the outbreaks.Clinical malaria cases in Ethiopia decreased by 80%, from 5.2 million cases (11% confirmed) in 2004 to 1.0 million cases (92% confirmed) in 2018; however, cases increased steadily to 2.6 million confirmed cases (98% confirmed) in 2022. Plasmodium vivax cases and proportion have increased significantly in the past 5 years. Clinical malaria hotspots are concentrated along the western Ethiopian border areas and have grown significantly from 2017 to 2022. Major malaria outbreaks in 2022/23 were detected in multiple sites across Ethiopia, and An. stephensi was the predominant vector in some of these sites, however, it was absence from many of the outbreak sites. Conclusions: The malaria burden has been significantly reduced in Ethiopia in the past two decades, but in recent years it has increased substantially, and the cause of such increase is a subject of further investigation. Major gaps exist in An. stephensi research, including vector ecology, surveillance, and control tools, especially for adult mosquito control.

A study to assess the nutritional status and dietary gap among pulmonary tuberculosis patients in Raipur city.

Background: Undernutrition raises the likelihood of progressing from tuberculosis (TB) infection to active TB illness and causes weight loss. Proper food and nutrition are important in the treatment of tuberculosis patients. Active tuberculosis necessitates a substantial energy expenditure. The Tuberculosis treatment guidelines neglect the nutritional supplementation part of Tuberculosis management. The study aims to determine the factors affecting the nutritional status of pulmonary Tuberculosis patients. Material and Methods: A hospital-based cross-sectional study was conducted from December 2021 to January 2022 among the patients newly diagnosed and above 18 years of age coming to DOTS Centre (DMC) of Pt J.N.M. Medical College, Raipur. Total 120 subjects were selected by consecutive sampling method. Data was analyzed using SPSS version 24, and P value <0.05 was considered statistically significant. Result: Among 120 study subjects, malnourished was 54.16% (BMI <18.50 kg/m2), normal was 35% (BMI 18.50-24.99 kg/m2), overweight was 6.67% (BMI 25-29.99 kg/m2), and obese were 4.17% (BMI 30-34.99 kg/m2). Among 120 study subjects, the maximum number of them (96.3%) had a dietary gap in their diets which was equal in two groups of 1-50% calorie deficit and 51-100% calorie deficit. Conclusion: A high proportion of tuberculosis patients were undernourished, and even a very distal factor for undernutrition became proximal for tuberculosis patients. To control tuberculosis and to end the tuberculosis disease, an improvement in the nutritional status of the patient should be our priority. By knowing the importance of nutrition in TB patients, the primary care physicians can decrease the morbidity and mortality in TB patients.

Investigating the optical properties and electronic structure of gallium phosphide nanotubes doped with arsenic via implementing first-principles calculations.

CONTEXT: This study investigates the impact of arsenic doping on the optical characteristics and electronic structure of zigzag (8, 0) and armchair (4, 4) gallium phosphide nanotubes using first-principles calculations based on the GaP1-xAsx system, where x = 0, 0.25, 0.5, 0.75, and 1. The electronic calculations showed that doping more arsenic atoms reduces the energy band gap for zigzag and armchair GaPAs nanotubes. PDOS analysis indicates that Ga-4p and P-3p orbitals play a significant role in determining the electronic properties of the GaP nanotube. The dominance of Ga-4p and P-3p orbitals in both the valence and conduction bands indicates their importance across the energy spectrum of the material. The complex dielectric function and absorption coefficient of zigzag and armchair GaP1-xAsx nanotubes are calculated for incident radiation with energies ranging from 1 to 6.2 eV. Optical results revealed that both zigzag and armchair GaPNTs exhibit strong absorption in the UV-visible regions due to electronic transitions between different Van Hove singularities. Also, due to quantum confinement effects, pure zigzag gallium phosphide nanotube exhibited two absorption edges at wavelengths (273 and 375 nm). These edges stand from the energy level's quantization in the nanotube construction, affecting the absorption characteristics. Substitutional doping by arsenic atoms changes the absorption edge to the long wavelengths due to decreased bandgap energy. Investigating electronic structures and optical properties of nanotubes proposes several advantages, such as understanding the doping effects on the nanotube structure and contributing to the direction of the experimental studies. These computational studies play a key role in developing the applications of nanomaterials. METHODS: Calculations of density functional theory (DFT) are achieved via the SIESTA package. SIESTA is a powerful and effective tool for executing DFT calculations on a large system of atoms. It generates numerous output files covering detailed information about the electronic structure, optical properties, total energy, optimized geometry, and other computed properties. The generalized gradient approximation GGA with Perdew-Burke-Ernzerhof PBE functional was used. A vacuum region of 10 A0 was applied to avoid the interactions of adjacent nanotubes.

Exposure to Crime and Racial Birth Outcome Disparities.

Urban communities in the United States were transformed at the end of the twentieth century by a rapid decline in neighborhood crime and violence. We leverage that sharp decline in violence to estimate the relationship between violent crime rates and racial disparities in birth outcomes. Combining birth certificate data from US counties with the FBI's Uniform Crime Reporting statistics from 1992 to 2002, we show that lower crime rates are associated with substantially smaller Black-White disparities in birth weight, low birth weight, and small for gestational age. These associations are stronger in more segregated counties, suggesting that the impacts of the crime decline may have been concentrated in places with larger disparities in exposure to crime. We also estimate birth outcome disparities under the counterfactual that the crime decline did not occur and show that reductions in crime statistically explain between one-fifth and one-half of the overall reduction in Black-White birth weight, LBW, and SGA disparities that occurred during the 1990s. Drawing on recent literature showing that exposure to violent crime has negative causal effects on birth outcomes, which in turn influence life-course outcomes, we argue that these results suggest that changes in national crime rates have implications for urban health inequality.

Structures and Functions of the Human GATOR1 Complex.

Eukaryotic cells coordinate available nutrients with their growth through the mechanistic target of rapamycin complex 1 (mTORC1) pathway, in which numerous evolutionarily conserved protein complexes survey and transmit nutrient inputs toward mTORC1. mTORC1 integrates these inputs and activates downstream anabolic or catabolic programs that are in tune with cellular needs, effectively maintaining metabolic homeostasis. The GAP activity toward Rags-1 (GATOR1) protein complex is a critical negative regulator of the mTORC1 pathway and, in the absence of amino acid inputs, is activated to turn off mTORC1 signaling. GATOR1-mediated inhibition of mTORC1 signaling is tightly regulated by an ensemble of protein complexes that antagonize or promote its activity in response to the cellular nutrient environment. Structural, biochemical, and biophysical studies of the GATOR1 complex and its interactors have advanced our understanding of how it regulates cellular metabolism when amino acids are limited. Here, we review the current research with a focus on GATOR1 structure, its enzymatic mechanism, and the growing group of proteins that regulate its activity. Finally, we discuss the implication of GATOR1 dysregulation in physiology and human diseases.

Using the GAP score as a complement to the new injury severity score in identifying severely injured patients- A registry-based cohort study of adult trauma patients in Sweden.

BACKGROUND: New Injury Severity Score (NISS) and Glasgow Coma Scale, Age and Pressure (GAP) scoring systems have cutoffs to define severe injury and identify high-risk patients. This is important in trauma quality monitoring and improvement. The overall aim was to explore if GAP scoring system can be a complement or an alternative to the traditional NISS scoring system. METHODS: Adults exposed to trauma between 2017 and 2021 were included in the study, using data from The Swedish Trauma Registry. The performance of NISS and GAP scores in predicting mortality, and ICU admissions were assessed using the area under the receiver operator characteristics (AUROC) in all patients and in subgroups (blunt, penetrating trauma and older (≥65 years) trauma patients). Patients were classified as severely injured by NISS >15 as Severely Injured NISS (SIN) or with a high-risk for mortality, by GAP 3-18 as High Risk GAP (HRG). Undertriage was calculated based on the cutoffs HRG and SIN. RESULTS: Overall, 37,017 patients were included. The AUROC (95 % CI) for mortality using NISS was 0.84 (0.83-0.85) and for GAP 0.92 (0.91-0.93) (p-value <0.001), the AUROC (95 % CI) for ICU-admissions was 0.82 (0.82-0.83) using NISS and for GAP 0.70 (0.70-0.71) p-value <0.001, in the overall cohort. In older patients the AUROC (95 % CI) for mortality was 0.76 (0.75-0.78) using NISS and 0.79 (0.78-0.81) using GAP, p-value <0.001. Overall, 8,572 (23.2 %) and 2,908 (7.9 %) were classified as SIN and HRG, respectively, with mortality rates of 13.7 % and 34.3 %. In the HRG group low-energy falls dominated and in the SIN group most patients were exposed to MVCs. In the SIN and HRG groups the rate of Emergency Trauma Interventions according to Utstein guidelines (ETIU) and ICU admission was 14.0 vs 9.5 % and 47.0 vs 62.5 % respectively. CONCLUSION: Our findings suggest that the GAP score and its cutoff 3-18 can be used to define severe trauma as complement to NISS >15 and can be a valuable tool in trauma quality monitoring and improvement. However, both scoring systems were less accurate in predicting mortality for the older trauma patients and should be explored further.

FANCM promotes PARP inhibitor resistance by minimizing ssDNA gap formation and counteracting resection inhibition.

Poly(ADP-ribose) polymerase inhibitors (PARPis) exhibit remarkable anticancer activity in tumors with homologous recombination (HR) gene mutations. However, the role of other DNA repair proteins in PARPi-induced lethality remains elusive. Here, we reveal that FANCM promotes PARPi resistance independent of the core Fanconi anemia (FA) complex. FANCM-depleted cells retain HR proficiency, acting independently of BRCA1 in response to PARPis. FANCM depletion leads to increased DNA damage in the second S phase after PARPi exposure, driven by elevated single-strand DNA (ssDNA) gap formation behind replication forks in the first S phase. These gaps arise from both 53BP1- and primase and DNA directed polymerase (PRIMPOL)-dependent mechanisms. Notably, FANCM-depleted cells also exhibit reduced resection of collapsed forks, while 53BP1 deletion restores resection and mitigates PARPi sensitivity. Our results suggest that FANCM counteracts 53BP1 to repair PARPi-induced DNA damage. Furthermore, FANCM depletion leads to increased chromatin bridges and micronuclei formation after PARPi treatment, elucidating the mechanism underlying extensive cell death in FANCM-depleted cells.

Retrospecting Digital Media Use, Negative Emotions, and Trust Gaps During the COVID-19 Pandemic in China: Cross-Sectional Web-Based Survey.

BACKGROUND: Retrospecting the trust gaps and their dynamics during the pandemic is crucial for understanding the root causes of postpandemic challenges and offers valuable insights into preparing for future public health emergencies. The COVID-19 pandemic eroded people's trust in strangers and acquaintances, while their trust in family members remained relatively stable. This resulted in 2 trust gaps, namely, the family members-strangers trust gap and the family members-acquaintances trust gap. Widening trust gaps impede social integration and undermine the effective management of public health crises. However, little is known about how digital media use shaped trust gaps during a pandemic. OBJECTIVE: This study aims to investigate the relationships between digital media use, negative emotions, the family members-strangers trust gap, and the family members-acquaintances trust gap during the COVID-19 pandemic in China. We test the mediating role of negative emotions between digital media use and 2 trust gaps and compare the indirect effect of digital media use on 2 trust gaps through negative emotions. METHODS: A cross-sectional web-based survey was conducted in China between January 31, 2020, and February 9, 2020. A total of 1568 adults participated in the survey. Questions related to digital media use, negative emotions, trust in family members, trust in acquaintances, and trust in strangers during the pandemic were asked. Regression analyses were performed to test the associations between the examined variables. We used a 95% bootstrap CI approach to estimate the mediation effects. RESULTS: Digital media use was positively associated with negative emotions (B=0.17, SE 0.03; P<.001), which in turn were positively associated with the family members-strangers trust gap (B=0.15, SE 0.03; P<.001). Likewise, digital media use was positively associated with negative emotions (B=0.17, SE 0.03; P<.001), while negative emotions were positively associated with the family members-acquaintances trust gap (B=0.08, SE 0.03; P=.01). Moreover, the indirect effect of digital media use on the family members-strangers trust gap (B=0.03, SE 0.01; 95% CI 0.01-0.04) was stronger than that on the family members-acquaintances trust gap (B=0.01, SE 0.01; 95% CI 0.003-0.027). CONCLUSIONS: The results demonstrate that negative emotions resulting from the frequent use of digital media are a key factor that accounts for the widening trust gaps. Considering the increasing reliance on digital media, the findings indicate that the appropriate use of digital media can prevent the overamplification of negative emotions and curb the enlargement of trust gaps. This may help restore social trust and prepare for future public health crises in the postpandemic era.

Patterns of connexin36 and eGFP reporter expression among motoneurons in spinal sexually dimorphic motor nuclei in mouse.

BACKGROUND: Sexually dimorphic spinal motoneurons (MNs) in the dorsomedial nucleus (DMN) and dorsolateral nucleus (DLN) as well as those in the cremaster nucleus are involved in reproductive behaviours, and the cremaster nucleus additionally contributes to testicular thermoregulation. It has been reported that MNs in DMN and DLN are extensively linked by gap junctions forming electrical synapses composed of connexin36 (Cx36) and there is evidence that subpopulation of MNs in the cremaster nucleus are also electrically coupled by these synapses. METHODOLOGY: We used immunofluorescence methods to detect enhanced green fluorescent protein (eGFP) reporter for Cx36 expression in these motor nuclei. RESULTS: We document in male mice that about half the MNs in each of DMN and DLN express eGFP, while the remaining half do not. Further, we found that the eGFP+ vs. eGFP- subsets of MNs in each of these motor nuclei innervate different target muscles; eGFP+ MNs in DMN and DLN project to sexually dimorphic bulbocavernosus and ischiocavernosus muscles, while the eGFP- subsets project to sexually non-dimorphic anal and external urethral sphincter muscles. Similarly, eGFP+ vs. eGFP- cremaster MNs were found to project to anatomically distinct portions of the cremaster muscle. By immunofluorescence, nearly all motoneurons in both DMN and DLN displayed punctate labelling for Cx36, including at eGFP+/eGFP+, eGFP+/eGFP- and eGFP-/eGFP- cell appositions. CONCLUSIONS: Most if not all motoneurons in DMN and DLN are electrically coupled, including sexually dimorphic and non-dimorphic motoneurons with each other, despite absence of eGFP reporter in the non-dimorphic populations in these nuclei that have selective projections to sexually non-dimorphic target muscles.

Association of connexin36 with adherens junctions at mixed synapses and distinguishing electrophysiological features of those at mossy fiber terminals in rat ventral hippocampus.

BACKGROUND: Granule cells in the hippocampus project axons to hippocampal CA3 pyramidal cells where they form large mossy fiber terminals. We have reported that these terminals contain the gap junction protein connexin36 (Cx36) specifically in the stratum lucidum of rat ventral hippocampus, thus creating morphologically mixed synapses that have the potential for dual chemical/electrical transmission. METHODOLOGY: Here, we used various approaches to characterize molecular and electrophysiological relationships between the Cx36-containing gap junctions at mossy fiber terminals and their postsynaptic elements and to examine molecular relationships at mixed synapses in the brainstem. RESULTS: In rat and human ventral hippocampus, many of these terminals, identified by their selective expression of vesicular zinc transporter-3 (ZnT3), displayed multiple, immunofluorescent Cx36-puncta representing gap junctions, which were absent at mossy fiber terminals in the dorsal hippocampus. In rat, these were found in close proximity to the protein constituents of adherens junctions (i.e., N-cadherin and nectin-1) that are structural hallmarks of mossy fiber terminals, linking these terminals to the dendritic shafts of CA3 pyramidal cells, thus indicating the loci of gap junctions at these contacts. Cx36-puncta were also associated with adherens junctions at mixed synapses in the brainstem, supporting emerging views of the structural organization of the adherens junction-neuronal gap junction complex. Electrophysiologically induced long-term potentiation (LTP) of field responses evoked by mossy fiber stimulation was greater in the ventral than dorsal hippocampus. CONCLUSIONS: The electrical component of transmission at mossy fiber terminals may contribute to enhanced LTP responses in the ventral hippocampus.

Evaluating well-being and psychosocial risks in academia: Is management the "forgotten phase"?

In recent years, there has been a noticeable increase in attention towards promoting well-being within academic settings. In the specific context of academia, a critical issue is understanding whether the current practices for assessing and managing well-being can bridge the implementation gap and increase opportunities for creating healthy academic conditions. The paper explores the practices adopted for assessing and managing work-related stress (WRS) risks in Italian academia by referring to data from a group of Italian universities of the QoL@Work network (Quality of Life at Work in academia). The aim is to improve understanding of the factors that influence the realization of a WRS risk assessment-management pathway and how they may facilitate or hinder the transition from assessment to the implementation of interventions in the academic context. The results suggest that the assessment-management pathway should prioritize the creation of organizational scaffolding to support participatory processes in order to prevent the data collected from failing to stimulate organizational change in working conditions.

Mind the Anion Gap: 5-Oxoproline-Induced High Anion Gap Metabolic Acidosis in End-Stage Renal Disease.

A rare complication, 5-oxoproline-induced high anion gap metabolic acidosis (HAGMA) is associated with chronic acetaminophen use, predominantly reported in outpatient settings. However, its occurrence in hospitalized patients, particularly those with end-stage renal disease (ESRD), remains underreported. We present a case of a 74-year-old female with ESRD on hemodialysis who developed HAGMA highly suspicious for 5-oxoproline toxicity from acetaminophen usage following cardiac surgery. Despite a standard analgesic dose, the patient's renal impairment likely predisposed her to 5-oxoproline accumulation, resulting in severe metabolic acidosis. Discontinuation of acetaminophen led to the resolution of HAGMA, highlighting the importance of recognizing this rare but potentially life-threatening complication in the inpatient and critical care setting. This case suggests a potential interaction between acetaminophen metabolism and renal dysfunction in the pathogenesis of 5-oxoproline-induced HAGMA.

Integrative analyses identified gap junction beta-2 as a prognostic biomarker and therapeutic target for breast cancer.

Background: Increasing evidence has shown that connexins are involved in the regulation of tumor development, immune escape, and drug resistance. This study investigated the gene expression patterns, prognostic values, and potential mechanisms of connexins in breast cancer. Methods: We conducted a comprehensive analysis of connexins using public gene and protein expression databases and clinical samples from our institution. Connexin mRNA expressions in breast cancer and matched normal tissues were compared, and multiomics studies were performed. Results: Gap junction beta-2 mRNA was overexpressed in breast cancers of different pathological types and molecular subtypes, and its high expression was associated with poor prognosis. The tumor membrane of the gap junction beta-2 mutated group was positive, and the corresponding protein was expressed. Somatic mutation and copy number variation of gap junction beta-2 are rare in breast cancer. The gap junction beta-2 transcription level in the p110α subunit of the phosphoinositide 3-kinase mutant subgroup was higher than that in the wild-type subgroup. Gap junction beta-2 was associated with the phosphoinositide 3-kinase-Akt signaling pathway, extracellular matrix-receptor interaction, focal adhesion, and proteoglycans in cancer. Furthermore, gap junction beta-2 overexpression may be associated with phosphoinositide 3-kinase and histone deacetylase inhibitor resistance, and its expression level correlated with infiltrating CD8+ T cells, macrophages, neutrophils, and dendritic cells. Conclusions: Gap junction beta-2 may be a promising therapeutic target for targeted therapy and immunotherapy and may be used to predict breast cancer prognosis.

Assessment of average femoral component rotation for balancing functionally aligned total knee replacement in varus deformity: Robotic image guidance study.

Introduction and purpose: Ensuring proper femoral component alignment post-Total Knee Arthroplasty (TKA) is crucial for normal patellofemoral (PF) kinematics. However, the customary 3° external rotation relative to the Posterior Condylar Axis (PC Axis) may not universally apply, and the expected final femoral component rotation remains unclear in functionally aligned knees. This study examines the relation between the Transepicondylar Axis (TEA) and PC axis, known as Posterior Condylar Angle (PCA) in Indian patients along with factors influencing PCA, and the feasibility of reproducing patient-specific PCA using image-guided Cuvis joint robot. Methods: Forty patients (52 Knees) with primary osteoarthritis and varus deformity were prospectively evaluated. Native PCA was determined using CT-based J planner. Pre-operative patellar shape, PF tilt, PF shift, final femoral component rotation (representing post-operative PCA), final patellar tracking, and post-operative functional and radiological assessment at 3 months were recorded. Results: Study participants averaged 64.3 years of age, with a female-to-male ratio of 23 to 17. Varus deformities varied, with IA2 being most prevalent, and sagittal plane deformities included fixed flexion (34.6 %) and hyperextension (44.2 %). The average PCA was 1.9° (range: 0°-7.3°), with most knees (41 out of 52) below 3°. The majority had Wiberg type 1 patellae, with pre-operative patellar tilt averaging 5.63°, reducing post-operatively to 4.43°. Most patients (37 out of 40) achieved excellent Knee Society functional scores at the 3-month mark. Complications included one case of delayed wound healing and one femoral array pin breakage. Notably, our study revealed a significant deviation in PCA from the commonly reported 3° in Western literature, underscoring the need for region-specific considerations in TKA planning. Conclusion: PCA of our population is statistically different from customary 3° followed with jig system. Image guided Robotics helps to identify patients specific PCA and reproducing the same was more commonly possible in patients with reducible Varus deformity.

The relationship between serum anion gap levels and short-, medium-, and long-term all-cause mortality in ICU patients with congestive heart failure: a retrospective cohort study.

BACKGROUND: There hasn't been research done on the connection between serum anion gap (AG) levels and long-, medium-, and short-term all-cause mortality in congestive heart failure (CHF) patients. This study aims to investigate the association between serum anion gap levels and all-cause mortality in CHF patients after adjusting for other covariates. METHODS: For each patient, we gather demographic information, comorbidities, laboratory results, vital signs, and scoring data using the ICU (Intensive Care Unit) Admission Scoring System from the MIMIC-III database. The connection between baseline AG and long-, medium-, and short-term all-cause mortality in critically ill congestive heart failure patients was investigated using Kaplan-Meier survival curves, subgroup analysis, restricted cubic spline, and Cox proportional risk analysis. RESULTS: 4840 patients with congestive heart failure in total were included in this study. With a mean age of 72.5 years, these patients had a gender split of 2567 males and 2273 females. After adjusting for other covariates, a multiple regression analysis revealed that, in critically ill patients with congestive heart failure, all-cause mortality increased significantly with rising AG levels. In the fully adjusted model, we discovered that AG levels were strongly correlated with 4-year, 365-day, 90-day, and 30-day all-cause mortality in congestive heart failure patients with HRs (95% CI) of 1.06 (1.04, 1.08); 1.08 (1.05, 1.10); and 1.08 (1.05, 1.11) (p-value < 0.05). Our subgroup analysis's findings demonstrated a high level of consistency and reliability. K-M survival curves demonstrate that high serum AG levels are associated with a lower survival probability. CONCLUSION: Our research showed the association between CHF patients' all-cause mortality and anion gap levels was non-linear. Elevated anion gap levels are associated with an increased risk of long-, medium-, and short-term all-cause death in patients with congestive heart failure. Continuous monitoring of changes in AG levels may have a clinical predictive role.

Osmolar gap in hyponatraemia: An exploratory study.

Hyponatraemia has indeed been extensively studied from multiple angles, including volume status, tonicity, and aetiology; however, the specific consideration of the osmolar gap (OG) within the context of hyponatraemia and its potential impact on their overall outcomes received limited attention in research. The current study represents an effort to address this gap in our understanding. This prospective exploratory study was conducted on adults aged 14 years and older at the Indus Hospital, Karachi, from 2017 to 2020. The study involved categorising severity of hyponatraemia and volume status. The osmolar gap (OG) was calculated and categorised as either increased (OG>10) or normal (OG<10). Among the 262 patients included in the study, there were 139 females and 123 males. Elevated OG was observed in 141(53.8%) patients. There were 28 (10.7%) recorded fatalities and majority of these individuals had an elevated OG. These findings underscore the importance for clinicians to consider the osmolar gap when managing patients with hyponatraemia.

A prognostic model incorporating the albumin-corrected anion gap in patients with aneurysmal subarachnoid hemorrhage.

Background: Aneurysmal subarachnoid hemorrhage (aSAH) patients typically have poor prognoses. The anion gap (AG) has been proven to correlate with mortality in various critically ill patients. However, hypoalbuminemia can lead to underestimations of the true anion gap levels. This study was conducted to verify the prognostic value of single AG and albumin-corrected anion gap (ACAG) among aSAH patients. Methods: Significant factors in the univariate logistic regression analysis were included in the multivariate logistic regression analysis to explore the risk factors for mortality in aSAH patients and to confirm the independent relationship between ACAG and mortality. The restricted cubic spline (RCS) was used to visually show the relationship between ACAG level and mortality risk of aSAH patients. The predictive model for mortality was developed by incorporating significant factors into the multivariate logistic regression analysis. The prognostic value of ACAG and the developed model was evaluated by calculating the area under the receiver operating characteristics curve (AUC). Results: Among 710 aSAH patients, a 30-day mortality was observed in 20.3% of the cases. A positive relationship was demonstrated between the ACAG level and mortality in aSAH patients using the RCS curve. The multivariate logistic regression analysis helped discover that only six factors were finally and independently related to mortality of aSAH patients after adjusting for confounding effects, including the Hunt-Hess scale score (p = 0.006), surgical options (p < 0.001), white blood cell count (p < 0.001), serum chloride levels (p = 0.023), ACAG (p = 0.039), and delayed cerebral ischemia (p < 0.001). The AUC values for the AG, albumin, and ACAG in predicting mortality among aSAH patients were 0.606, 0.536, and 0.617, respectively. A logistic regression model, which includes the Hunt-Hess scale score, surgical options, white blood cell count, serum chloride levels, ACAG, and delayed cerebral ischemia, achieved an AUC of 0.911 for predicting mortality. Conclusion: The ACAG is an effective prognostic marker for aSAH patients. A prognostic model incorporating ACAG could help clinicians evaluate the risk of poor outcomes among aSAH patients, thereby facilitating the development of personalized therapeutic strategies.

Cx40 Levels Regulate Hypoxia-Induced Changes in the Migration, Proliferation, and Formation of Gap Junction Plaques in an Extravillous Trophoblast Cell Model.

BACKGROUND: Extravillous trophoblasts (EVTs) form stratified columns at the placenta-uterus interface. In the closest part to fetal structures, EVTs have a proliferative phenotype, whereas in the closest part to maternal structures, they present a migratory phenotype. During the placentation process, Connexin 40 (Cx40) participates in both the proliferation and migration of EVTs, which occurs under hypoxia. However, a possible interaction between hypoxia and Cx40 has not yet been established. METHODS: We developed two cellular models, one with "low Cx40" (Jeg-3), which reflected the expression of this protein found in migratory EVTs, and one with "high Cx40" (Jeg-3/hCx40), which reflected the expression of this protein in proliferative cells. We analyzed the migration and proliferation of these cells under normoxic and hypoxic conditions for 24 h. Jeg-3 cells under hypoxia increased their migratory capacity over their proliferative capacity. However, in Jeg-3/hCx40, the opposite effect was induced. On the other hand, hypoxia promoted gap junction (GJ) plaque formation between neighboring Jeg-3 cells. Similarly, the activation of a nitro oxide (NO)/cGMP/PKG-dependent pathway induced an increase in GJ-plaque formation in Jeg-3 cells. CONCLUSIONS: The expression patterns of Cx40 play a crucial role in shaping the responses of EVTs to hypoxia, thereby influencing their migratory or proliferative phenotype. Simultaneously, hypoxia triggers an increase in Cx40 gap junction (GJ) plaque formation through a pathway dependent on NO.

CO2 gap changes compared with cardiac output changes in response to intravenous volume expansion and/or vasopressor therapy in septic shock.

Background: The difference in partial pressure of carbon dioxide (PCO2) between mixed or central venous blood and arterial blood, known as the ∆PCO2 or CO2 gap, has demonstrated a strong relationship with cardiac index during septic shock resuscitation. Early monitoring of the ∆PCO2 can help assess the cardiac output (CO) adequacy for tissue perfusion. Objectives: To investigate the value of ∆PCO2 changes in early septic shock management compared with CO. Methods: This observational prospective study included 76 patients diagnosed with septic shock admitted to Cairo University Hospital's Critical Care Department between December 2020 and March 2022. Patients were categorised by initial resuscitation response, initial ∆PCO2 and 28-day mortality. The primary outcome was the relationship between the ∆PCO2 and CO changes before and after initial resuscitation, with secondary outcomes including ICU length of stay (LOS) and 28-day mortality. Results: Peri-resuscitation ∆PCO2 changes predicted a ≥15% change in the cardiac index (CI) (area under the curve (AUC) 0.727; 95% CI 0.614 - 0.840) with 66.7% sensitivity and 62.8% specificity. The optimal ∆PCO2 change cut-off value was <-1.85, corresponding to a <-22% threshold for a 15% cardiac index increase. The PCO2 gap ratio (gap/gap ratio of T1- PCO2 gap to T0 -PCO2 gap) also predicted a ≥15% change in cardiac index (AUC 745; 95% CI 0.634 - 0.855) with 63.6% sensitivity and 79.1% specificity. The optimal CO2 gap/gap ratio cut-off value was <0.71. A significant difference in 28-day mortality was noted based on the gap/gap ratio. Conclusion: Peri-resuscitation ∆PCO2 and the gap/gap ratio are useful non-invasive bedside markers for predicting changes in CO and preload responsiveness. Contribution of the study: The current study provides an insight to the PCO2 gap changes during and after early resuscitation of septic shock patients, which correlate to cardiac output changes and might also serve as a fluid responsiveness indicator.